Symptoms and General Pathology

All Conditions

Immune System Diseases

Inflammation

Autoimmune Diseases

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Atezolizumab

Immune Checkpoint Inhibitors

Avelumab

Durvalumab

Cemiplimab

Ipilimumab

Marie Hudson, MD

Manuel Flores, PhD

Marie Hudson, MD MPH

Immune checkpoint inhibitors (ICI) are among the most promising approaches to fighting cancer. However, a substantial percentage of patients experience off-target adverse effects in the form of mild to severe inflammation in different organs, commonly called immune-related adverse events (irAEs). irAEs can lead to treatment discontinuation, or can be life-threatening in extreme cases. The causes of irAEs are largely unknown and there are no reliable predictive biomarkers. The Montreal Immune-Related Adverse Events (MIRAE) study collects clinical information and biospecimens (blood, tissue, stool) from cancer patients treated with ICI to facilitate research on the identification of predictive biomarkers of irAEs, their causes, and the design of effective management strategies.

Background:

During cancer development and progression, cancer cells evolve to evade natural anti-tumor immunity. One major pathway of immune evasion involves the engagement of co-inhibitory receptors present on the surface of T cells that modulate their activation status, and therefore their ability to directly or indirectly kill tumor cells. These receptors are known as immune checkpoint inhibitors (ICI). Blockade of ICI using antibodies leads to prolonged T cell activation and unleashes the anti-tumor activity of T cells. ICI treatment for cancer has led to unprecedented advances in cancer treatment by prolonging survival of patients with previously refractory cancers. Among these ICI, CTLA-4, PD-1 and PDL-1 inhibitors have been shown to be effective cancer immunotherapies, and many other ICIs are now in pre-clinical and clinical development.

Although ICI cancer therapy is overall well tolerated, off-target immune reactions targeting healthy cells or tissues called immune-related adverse events (irAEs) develop in a substantial percentage of patients limiting the use of ICI therapy. irAEs target range from mild to severe and fatal. Currently, there are no reliable predictive biomarkers for the wide spectrum of irAEs and their clinical management in severe cases involves discontinuation of ICI therapy.

The Montreal Immune-Related Adverse Events (MIRAE) study is a biobank that collects human biological specimens (e.g., tissue, blood, plasma, PBMCs, saliva, stool) and the associated clinical information from cancer patients treated with ICI with the purpose of promoting research to identify clinical and biological predictors and mechanisms of irAEs, evaluate the effects of immunomodulatory treatment of irAEs on tumor biology, and investigate treatment strategies to minimize irAEs.

Objectives:

1. Identify biomarkers predictive of irAEs, including cellular, immunologic, genetic and microbial biomarkers; and
2. Evaluate the effects of immunomodulatory treatment of irAEs, and investigate treatment strategies that minimize irAEs and maximize ICI efficacy.

* Whole blood
* Peripheral blood mononuclear cells
* Stool
* Tissue biopsies

Montreal Immune-Related Adverse Events (MIRAE) Study

Montreal Database and Biorepository of Cancer Patients Treated With Immune Checkpoint Inhibitors for the Study of Immune-related Adverse Events

Sir Mortimer B. Davis - Jewish General Hospital

Marie Hudson, MD MPH FRCPC Principal Investigator, Rheumatologist, Division of Rheumatology and Department of Medicine, Jewish General Hospital and McGill University

Blood and Lymph Conditions

Hematologic Diseases

Patients and healthy normal volunteers undergo collection of peripheral blood samples for analysis via flow cytometry, RNASeq, immunohistochemistry, CyTOF experiments, cell cultures, and functional studies of immune cell subsets obtained by FACS. Patients also undergo collection of bone marrow and leukopheresis/leukoreduction specimens, and single cell suspensions and bulk excised tumor biopsies are obtained from routine testing for analysis via immunohistochemistry or CyTOF.

Undergo collection of peripheral blood, bone marrow, and tissue

Biospecimen Collection

Laboratory Biomarker Analysis

Questionnaire Administration

Arta Zenunovic

Akil A. Merchant, MD

Casey O'Connell, MD

This research trial collects and stores blood, tissue, and bone marrow specimens from patients with cancer or blood disorders, and healthy volunteers to study the immune system in a variety of different types of experiments, as well as associated clinical data as appropriate, focused on understanding mechanisms of immunotherapy.

PRIMARY OBJECTIVES; I. Identify changes in immune system parameters in patients receiving immunotherapies (including immune checkpoint inhibitors, immunostimulatory/immunomodulatory agents, cellular therapies, stem cell transplantation) and compare to changes in patients receiving conventional chemotherapy, targeted-agent therapy, and healthy normal volunteers using multiparameter flow cytometry, time-of-flight mass cytometry, cytokine quantification, functional analysis of immune cell subsets isolated via fluorescence activated cell sorting (FACS), and genetic and proteomic techniques (deoxyribonucleic acid \[DNA\] sequencing, ribonucleic acid sequence \[RNASeq\], reverse transcriptase-polymerase chain reaction \[RT-PCR\], Western blot).

SECONDARY OBJECTIVES:

I. Optimize methods for measuring functional status of circulating immune cells and hematopoietic progenitors (activation, inhibition, cytotoxicity, proliferative capacity).

II. Use genetic and epigenetic techniques to a) study clonal diversity in T cell subsets b) determine the genetic basis for T cell immune reconstitution following stem cell transplantation.

OUTLINE:

Patients and healthy normal volunteers undergo collection of peripheral blood samples for analysis via flow cytometry, RNASeq, immunohistochemistry, cytometry by time of flight (CyTOF) experiments, cell cultures, and functional studies of immune cell subsets obtained by FACS. Patients also undergo collection of bone marrow and leukopheresis/leukoreduction specimens, and single cell suspensions and bulk excised tumor biopsies are obtained from routine testing for analysis via immunohistochemistry or CyTOF.

After completion of study, patients are followed up for up to 2 years.

Collection of Immunology Specimens From Patients With Cancer or Blood Disorders, and Healthy Volunteers

Protocol for Immunology Specimen Collection From Cancer Patients, Patients With Hematologic Diagnoses, and Healthy Normal Controls

Tissue, blood, and bone marrow samples collected will be used to identify changes in immune system parameters in patients receiving immunotherapies (including immune checkpoint inhibitors, immunostimulatory/immunomodulatory agents, cellular therapies, stem cell transplantation) and compare to changes in patients receiving conventional chemotherapy, targeted-agent therapy, and healthy normal volunteers using multiparameter flow cytometry, time-of-flight mass cytometry, cytokine quantification, functional analysis of immune cell subsets isolated via fluorescence activated cell sorting (FACS), and genetic and proteomic techniques (deoxyribonucleic acid \[DNA\] sequencing, ribonucleic acid \[RNA\]-sequence \[Seq\], reverse transcriptase-polymerase chain reaction \[RT-PCR\], Western blot).

National Cancer Institute (NCI)

University of Southern California

Infections

Respiratory Tract (Lung and Bronchial) Diseases

Neoplasms

Heart and Blood Diseases

Rare Diseases

COVID-19

Multiple Myeloma

Neoplasms, Plasma Cell

Waldenstrom Macroglobulinemia

Pneumonia

Pneumonia, Viral

Communicable Diseases

Respiratory Tract Infections

Virus Diseases

Coronavirus Infections

Coronaviridae Infections

Nidovirales Infections

RNA Virus Infections

Lung Diseases

Respiratory Tract Diseases

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Vaccines

People with Multiple Myeloma-MM receiving covid 19 vaccine

People with Waldenstrom's macroglobulinemia-WM receiving covid 19 vaccine categorized by treatment naïve, actively receiving BTK inhibitor,currently or previously treated.

Andrew Branagan, MD, PhD

Clifton Mo, MD

This research is being done to see if the immune (defense) system of people with Multiple Myeloma and Waldenstrom's Macroglobulinemia reacts to the COVID-19 vaccine.

COVID-19 vaccines are designed to help prevent infections, hospitalizations, and death from the COVID-19 virus. Normally, when the vaccine is administered, the immune system reacts by creating antibodies (proteins made by the body's immune system to fight infections such as COVID-19) and helping the immune system's blood cells to fight it. In people with Multiple Myeloma and Waldenstrom's Macroglobulinemia, their immune system does not function normally, and an effective immune response may not occur. The research study procedures include screening for eligibility and the collection of data and biospecimens. It is expected that about 160 people will take part in this research study.

Blood drawn for routine and covid antibody testing

Covid-19 Vaccine Responsiveness in MM and Waldenstrom

Covid-19 Vaccine Responsiveness in Patients With Multiple Myeloma and Waldenstrom's Macroglobulinemia

The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

The primary endpoint is the effective immune response (EIR) rate at 28 days following the second or final vaccine dose. EIR will be defined by a positive SARS-CoV-2 spike antibody index (S/C). The EIR rate will be reported along with the exact 95% confidence interval.

Massachusetts General Hospital

Principal Investigator

Lymphoma

Lymphoma, Non-Hodgkin

Lymphoma, Large B-Cell, Diffuse

Lymphoma, B-Cell

Lymphosarcoma

B-cell Lymphoma

Immunomodulating Agents

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of lisocabtagene maraleucel. During lisocabtagene maraleucel production, subjects may receive low-dose chemotherapy for disease control. Upon successful generation of lisocabtagene maraleucel product, subjects will receive treatment which will include lymphodepleting chemotherapy followed by one dose of lisocabtagene maraleucel administered by intravenous (IV) injection.

lisocabtagene maraleucel will be administered as single dose intravenous (IV) injection

lisocabtagene maraleucel

Bristol-Myers Squibb

This is an open-label, multicenter, Phase 2 study to determine the safety, PK, and efficacy of lisocabtagene maraleucel (JCAR017) in subjects who have relapsed from, or are refractory to, two lines of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) in the outpatient setting. Subjects will receive treatment with JCAR017 and will be followed for up to 2 years.

This is an open-label, multicenter, Phase 2 study to assess the safety and antitumor activity in adult patients with relapsed or refractory B-cell non-Hodgkin Lymphoma when administered with lisocabtagene maraleucel (JCAR017) in the outpatient setting.

Upon the successful product generation of lisocabtagene maraleucel, subjects will enter the treatment phase of the study. Treatment will include lymphodepleting chemotherapy followed by lisocabtagene maraleucel administration. Subjects will then enter the post-treatment follow-up phase of the study and will be followed for approximately 24 months for safety, disease status, health-related quality of life (HRQoL), and survival. Long-term follow-up will continue under a separate long-term follow-up protocol, per health regulatory authority guidelines, currently up to 15 years after the last lisocabtagene maraleucel administration.

A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)

A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting

Information relating to our policy on data sharing and the process for requesting data can be found at the following link:

https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Cytokine release syndrome is characterized by high fever, fatigue, nausea, headache, dyspnea, tachycardia, rigors, hypotension, hypoxia, myalgia/arthralgia, and anorexia.

Incidence of Grade ≥ 3 CRS, based on the TEAE with MedDRA PT "Cytokine release syndrome," graded according to the grading scale adapted from Lee (Lee 2014).

NT events have also been reported and may include neurologic symptoms such as altered mental status, aphasia, altered level of consciousness, and seizures or seizure-like activity.

Incidence of Grade ≥ 3 NT, defined as an Investigator-identified TEAE considered neurotoxicity related to JCAR017.

Incidence of treatment-emergent Grade ≥ 3 infections, defined using MedDRA SOC.

Prolonged cytopenia is defined as the occurrence of Grade ≥ 3 cytopenia not resolved by the Day 29 visit, based on laboratory results of low hemoglobin, absolute neutrophil count decreased, and platelet count decreased. The frequency of subjects experiencing each individual laboratory abnormality and the total number with at least 1 abnormality will be summarized, as will recovery from prolonged cytopenia after Day 29.

The Percentage of participants with a best overall response (BOR) of either CR or PR based on the Lugano 2014 criteria.

Disease response will be determined according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

Complete response is defined as:

1. Score 1, 2, or 3a with or without residual mass
2. No evidence of FDG-avid disease in marrow

Partial Response is defined as:

1. Score 4 or 5a with reduced uptake compared with baseline and residual masses of any size
2. Bone marrow with residual uptake higher than in normal marrow but reduced compared with baseline (diffuse uptake compatible with reactive changes from chemotherapy allowed). If there are persistent focal changes in marrow in the context of a nodal response, should consider further evaluation with MRI, biopsy, or interval scan.

The Percentage of participants with a best overall response (BOR) with CR based on the Lugano 2014 criteria.

Disease response will be determined according to the "Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification"

Complete response is defined as:

1. Score 1, 2, or 3a with or without residual mass
2. No evidence of FDG-avid disease in marrow

Duration of response (DOR) is defined as the time from the first documentation of response (CR or PR) after JCAR017 infusion to disease progression or death from any cause, whichever occurs first.

Duration of response (DOR) if BOR is CR is defined for subjects with a BOR of CR as the time from the first documentation of response (CR or PR) after JCAR017 infusion to earlier of disease progression or death from any cause.

Progression-free survival is defined as the time from infusion of JCAR017 to progressive disease or death, whichever is earlier. If a subject does not have an event for the PFS analysis, the subject will be censored.

Progressive Disease is defined as:

1. Score 4 or 5a with an increase in intensity of uptake from nadir
2. New FDG-avid foci consistent with lymphoma (may need biopsy or repeat scan if uncertain about etiology of foci).
3. Investigator assessed clinical progression

Overall survival is defined as the time from infusion of JCAR017 to the date of death. For assessment of OS, data from surviving participants will be censored at the last time that the participant is known to be alive. The OS analysis will include all available survival information from the long-term follow-up study if applicable.

The EORTC QLQ-C30 is a 30-item scale composed of both multi-item scales and single-item measures. All of the scales and single-item measures range in score from 0 to 100. A higher scale score represents a higher level of well-being and better ability of daily functioning. Thus, a high score for a functional scale represents a high/healthy level of functioning; a high score for the global health status/HRQoL represents a high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatic problem.

EQ-5D is a standardized measure of health status developed by the EuroQol Group in order to provide a simple, generic measure of health for clinical and economic appraisal. The EQ-5D-5L consists of the EQ-5D-5L descriptive system and the EQ Visual Analogue scale (EQ VAS). The descriptive system comprises dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). Each dimension has 5 levels (no problems, slight problems, moderate problems, severe problems, and extreme problems).

Length of initial ICU and non-ICU stay from liso-cel administration

Juno Therapeutics, a Subsidiary of Celgene

The total number at risk for all-cause mortality represents all participants who underwent leukapheresis. The total number at risk by any serious adverse event and other (not including serious) adverse events represents all participants that received at least 1 dose of study medication (JCAR017).

Participants underwent leukapheresis and may receive salvage low- dose chemotherapy or one cycle of non-curative standard of care antitumor therapy if required. Eligible participants then received lymphodepleting chemotherapy with fludarabine and cyclophosphamide (flu/cy) followed by a single dose of JCAR017 (100×10\^6 CAR+ T cells/infusion) administered intravenously (IV) 2 to 7 days after completion of lymphodepleting chemotherapy.

Lisocabtagene Maraleucel (JCAR017)

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

White

Other

Unknown

Race/Ethnicity, Customized

Bristol-Myers Squibb Study Director

All participants who received at least one JCAR017 infusion

Percentage of Participants With Cytokine Release Syndrome (CRS) Adverse Events Grade ≥ 3

Percentage of Participants With Neurotoxicity (NT) Adverse Events Grade ≥ 3

Percentage of Participants With Infection Adverse Events Grade ≥ 3

Percentage of Participants With Prolonged Grade ≥ 3 Cytopenia at Day 29.

Number of Participants With Adverse Events

Number of Participants With Clinically Significant Laboratory Abnormalities- Hematology

Number of Participants With Clinically Significant Laboratory Abnormalities- Chemistry

Number of Participants With Adverse Events Grade ≥ 3

Time to Onset

Time to Resolution

Time to Onset and Time to Resolution of Grade ≥ 3 Cytokine Release Syndrome (CRS)

Time to Onset and Time to Resolution of Grade ≥ 3 Neurotoxicity (NT)

Tocilizumab Only

Corticosteroid Only

Both Tocilizumab and Corticosteroid

Number of Participants Administered Tocilizumab and Corticosteroid for Management of Cytokine Release Syndrome (CRS)

Number of Participants Administered Tocilizumab and Corticosteroid for Management of Neurotoxicity (NT)

Objective Response Rate (ORR)

Complete Response Rate (CRR)

DoCR

Duration of Response (DoR) and Duration of Complete Response (DoCR)

Progression Free Survival (PFS)

Overall Survival (OS)

Area Under the Blood Concentration-time Curve From Time to Zero to 28 Days After Dosing AUC (0-28)

Maximum Observed Blood Concentration (Cmax)

Time of Maximum Observed Blood Concentration (Tmax)

European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30

EuroQol Instrument EQ-5D-5L.

Initial ICU Stay

Initial Non-ICU Stay

Liso-cel-treated Analysis Set - Inpatient Monitored

Number of Intensive Care Unit (ICU) Inpatient Days and Non-ICU Inpatient Days and Reasons for Hospitalization

Number of Participants Transfused and the Number of Transfusions Per Participant.

Number of Participants Requiring Growth Factor Support.

Number of Participants Requiring Intravenous Immunoglobulin (IVIG) Support

Pre-Treatment Phase

Treatment Phase

Diseases and Abnormalities at or Before Birth

Hemoglobinopathies

Genetic Diseases, Inborn

Subjects with a diagnosis of hemoglobinapathy except Sickle Cell Disease

Subjects with a diagnosis of Sickle Cell Disease

Oncology diagnosis with involvement of the neurological system

Subjects with any oncology diagnosis except those that involve the neurological system.

Subjects who have received or are intending to have a stem cell transplant for treatment of disease.

Prakash Satwani, MD

New York City (NYC) has become the epicenter of the worldwide pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). By collecting and summarizing the experience with other major health care providers in the tristate (New York (NY), New Jersey (NJ) and Connecticut (CT)) are, the investigators are uniquely positioned to inform the rest of the country about what to expect and how to manage children and young adults with hematological, oncological or stem cell transplant diagnoses during the pandemic.

The subjects are all pediatric hematology, oncology or stem cell transplant (HOT) children and young adults who are tested for SARS-CoV-2. The investigators will collect data including demographics, clinical characteristics, clinical courses, outcomes from the medical record.

Other information about finances, mental health, and nutrition will be ascertained by questionnaires. The subjects will be asked to allow the researchers to abstract information from their medical record, participate in an interview or telephone call (their choice) to answer questionnaires, and to provide a stool sample at three time points.

The creation of an integrated database of COVID-19 pediatric and young adult patients will better inform the pediatric hematology, oncology, and stem cell transplant community about this disease specifically related to patients undergoing HOT therapy and provide valuable evidence to develop standardized and clinically appropriate approaches to their care.

Optional stool specimens may be collected at three time points: 1) at diagnosis, 2) at resolution of COVID-19, 3) and at six months post-diagnosis.

Pediatrics HOT COVID-19 Database in NY Tristate

Retrospective and Prospective Database of COVID-19 Prevalence and Clinical Course in Pediatric and Young Adult Hematology/ Oncology/Stem Cell Therapy Patients in the New York Tri-State Area.

To measure the success of the data registry in how many patients agreed to participate and completed the one year follow up. A confirmed case of COVID-19 is defined as a positive result on a reverse-transcriptase- polymerase-chain-reaction (RT-PCR) assay of a specimen collected on a nasopharyngeal swab, or a serum antibody test. Only laboratory-confirmed cases will be described as positive.

To analyze effect of COVID-19 on patients and their families mental health. PROMIS® (Patient-Reported Outcomes Measurement Information System) is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. Each item on the measure is rated on a 5-point scale (1=never; 2=rarely; 3=sometimes; 4=often; and 5=always) with a range in score from 8 to 40 with higher scores indicating greater severity of depression.

To examine if the pandemic has effects on the patients' nutrition and microbiome. Each patient is given an opportunity to provide stool samples in addition to survey response.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Montreal Immune-Related Adverse Events (MIRAE) Study	NCT05139706	Cancer Immune System D... Inflammatory Re... Autoimmune Dise...		18 Years - 100 Years	Sir Mortimer B. Davis - Jewish General Hospital
Collection of Immunology Specimens From Patients With Cancer or Blood Disorders, and Healthy Volunteers	NCT03207854	Healthy Subject Hematologic and... Hematopoietic a... Immune System D... Malignant Neopl...	Biospecimen Col... Laboratory Biom... Questionnaire A...	19 Years -	University of Southern California
Covid-19 Vaccine Responsiveness in MM and Waldenstrom	NCT04830046	Multiple Myelom... Waldenstrom Mac... Immune System D... Covid19		18 Years -	Massachusetts General Hospital
Covid-19 Vaccine Responsiveness in MM and Waldenstrom	NCT04830046	Multiple Myelom... Waldenstrom Mac... Immune System D... Covid19		18 Years -	Massachusetts General Hospital
Montreal Immune-Related Adverse Events (MIRAE) Study	NCT05139706	Cancer Immune System D... Inflammatory Re... Autoimmune Dise...		18 Years - 100 Years	Sir Mortimer B. Davis - Jewish General Hospital
A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)	NCT03744676	Lymphoma, Non-H... Lymphoma Lymphoma, B-Cel... Lymphoma, Large... Neoplasms Neoplasms by Hi... Lymphoprolifera... Lymphatic Disea... Immunoprolifera... Immune System D...	lisocabtagene m...	18 Years -	Juno Therapeutics, a Subsidiary of Celgene
Pediatrics HOT COVID-19 Database in NY Tristate	NCT04445402	Pediatric Cance... Immune System D... COVID-19 Hemoglobinopath...		- 21 Years	Columbia University

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